Contents:

Conference Topics 8:50 Chairperson's Opening Remarks Radislav A. Potyrailo, PhD, Biosciences, Combichemistry and Characterization Technologies, Global Research Center, General Electric Company 9:00 KEY NOTE ADDRESS Exploiting the Innovator's Dilemma Eric J. Amis, PhD, Chief, Polymers Division, National Institute of Standards and Technology When new innovation emerges, it is reasonable that the current technical leaders would be in the best position to capitalize on it. These leaders typically have the most resources, the best ties to the community, and the expertise to know how to promote new breakthroughs. In his provocative book, The Innovator's Dilemma: When New Technologies Cause Great Firms to Fail (Harvard Business School Press, 1997), Clayton Christensen showed that precisely because of these supposed advantages, many successful and well-run companies fail miserably when faced with radical innovations. Among other things, they fail see how breakthroughs that initially yield worse performance can disrupt, and ultimately displace, conventional expertise. If "Combi" is a disruptive innovation, how can we succeed? 9:45 HTE in Polymer Research: Parallel Synthesis, Advanced Characterization and Thin Film Library Preparation Ulrich S. Schubert, PhD, Professor, Dutch Polymer Institute and Laboratory or Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology, The Netherlands Automated synthesizers were successfully utilized for controlled and living polymerizations in solution, bulk and in emulsion (CROP, ATRP, RAFT, anionic, etc.). For this purpose, online and offline investigations utilizing GC, GPC, NMR and MALDI-TOF-MS were developed. In addition, combinatorial methods for defined spot and film preparation utilizing ink-jet printing as well as automated methods for the characterization of thin films, such as plate readers or AFM, were investigated. Finally, the data-handling, data-mining and modeling of the complete workflow will be presented together with selected applications for catalysts optimization and coating developments. 10:45 KEY NOTE ADDRESS Connecting High-Throughput Experimentation and Predictive Models in Catalyst Screening Peter Chen, PhD, Professor of Physical-Organic Chemistry, ETH Zürich, Switzerland High-throughput experimentation and combinatorial methods produce large amounts of data. Data reduction usually means data mining, i.e. the search for "hits" that jump out from the baseline using some sort of search and visualization routine. Complicated physical or chemical phenomena, such as materials properties or catalyst activity or selectivity, however, typically depend on a many parameters which may mutually compensate or cancel. Accordingly, it is often the case that the correlations are not evident from the data themselves. Quantitative modeling of the data provides an efficient route to extraction of parameters in predictive models from the data produced by HTE. 11:30 Latest Progress in Oxidation and Polymerization High Throughput Screening Gert-Jan Gruter, PhD, Professor, Vice President, Avantium Chemicals, The Netherlands The real value of High Throughput Screening (HTS) for clients is in the increased rate of innovation and the reduced time-to-market for new products and processes. This will be illustrated via case studies around fixed bed and batch catalyst screening for selective alkane oxidation (propane to acrylic acid, cyclohexane to cyclohexanone cyclohexanol) and examples generated with our new state-of-the art secondary screening polyolefins platform. Avantium offers contract research services whereby work is executed in close colaboration with the clients' scientific, engineering and business staff, to build a seamless project team acting as an extension of the client's R&D capabilities. 2:00 Microrheology as a Tool for High-Throughput Screening David J. Pine, PhD, Professor & Chair of Chemical Engineering, Professor of Materials, University of California, Santa Barbara Microrheology can be use as a tool to screen the rheological properties of libraries of gels and other complex fluids. Either multiple light scattering or video microscopy techniques can be used to probe sample volumes of 1 nl to 1 µl. The two methods complement each other and the choice of which to use depends on the properties of the samples. We illustrate the potential of this approach to high throughput screening with aqueous solutions of a block co-polypeptide library and the rheological phase diagram of a water/surfactant/salt. 2:30 Droplet Compartmentalization and Manipulation of Fluids in Microfluidic Devices Darren R. Link, PhD, Postdoctoral Fellow, Weitz Laboratory, Harvard University Compartmentalization of fluid components in microreactors is accomplished by the controlled formation of droplets of precise composition in microfluidic devices. Two different types of droplets are generated independently and then brought together to initiate chemical reactions at a precise location. Control over the timing of droplet formation and the manipulation of the drops is accomplished through electrostatic charging of the drops and application of electric fields. 3:00 Formulations Informatics Michael Doyle, PhD, Accelrys Materials Informatics Team, Accelrys Formulation is critical to adding value in today’s detergents businesses. It is a key process by which these businesses create new and improved products using existing manufacturing methods and materials. Good formulation design matches customer needs with available technologies, controls costs, resolves manufacturing issues, and ensures compliance with regulations. These goals often conflict and must be balanced. Formulation is thus a complex and difficult process, heavily reliant on the expertise of individual formulators. The volumes of data in experimental programs of high throughput formulation is staggering. In fact they are so large that a software framework is required to manage and choose the optimum pathway to a solution. We have developed an approach to the management and analysis of this volume of data. The software comprises several individual, but integrated "Tools", and so is called FAST (the "Formulation-Assisting Software Toolkit". Using FAST, we have examined a set of designed experiments focused on exploring detergent lather by varying the surfactant sub-system. FAST supports knowledge management in that any of the knowledge generated in the above steps is shared through a database, and so is accessible to multiple users. However, in this talk we will focus on the details of the statistical and optimization methods used. 4:00 Combinatorial Methods for Pharmaceutical Development Eric Carlson, PhD, Group Leader Discovery Tools Chemistry, Symyx Technologies, Inc. We have developed several combinatorial workflows for pharmaceutical development that facilitate entire high throughput workflows from experimental design, to sample preparation, to screening, to data analysis and querying. The workflows described allow one to conduct parallel arrays of experiments using small quantities of material and are directed at the search for novel salt forms, novel polymorphic forms, and novel formulations, and at profiling the solubility and stability of drug compounds. 4:30 Automated Development of Complex Materials: Concept vs. Practice Yadunandan L. Dar, Corporate Research, National Starch and Chemical Company The vision for the automated formulation and testing of complex commercially viable materials to generate higher throughput and reliability is very powerful for most chemicals and materials industries. This talk will discuss thought provoking scenarios applicable to the translation of industrial testing methodolgy to combinatorial or high throughput approaches. It addresses technical and non-technical issues important for success. 5:00 High-Throughput Measurements of Immiscible Fluids Steven D. Hudson, PhD, Physical Scientist, Polymers Division, National Institute of Standards and Technology We describe a new microfluidic system to evaluate important properties of libraries of immiscible fluid mixtures, comprising oil, water, surfactants and other additives. Using techniques for fluid mixing and drop formation, together with online image and particle-tracking analysis that measures the deformation of drops, and their speed as they are convected through an extensional flow field, the composition-dependent interfacial tension can be measured rapidly. In collaboration with: J. T. Cabral, K. L. Beers, T. Wu, A. Karim, E. J. Amis, NIST 8:55 Chairperson's Remarks Ulrich S. Schubert, PhD, Professor, Dutch Polymer Institute and Laboratory or Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology, The Netherlands 9:00 KEY NOTE ADDRESS Application of High-Throughput Methodologies to Material Discovery W. Henry Weinberg, PhD, Senior Vice President and CTO, Symyx Technologies, Inc., and Michael A. Nemzek, PhD, General Manager Symyx Discovery Tools, Symyx Technologies, Inc. Despite the recent press about the low return on investment from high-throughput experimentation and combinatorial approaches taken in pharmaceutical discovery research in the 1990’s, high-throughput combinatorial technologies in the materials sciences field are showing great promise, with several examples of early success in a much shorter timeframe. Examples of the parallels and divergences of combinatorial approaches between pharmaceutical and materials discovery will be discussed. The unique Symyx approach to high throughput combinatorial materials discovery and some examples of recent successes from Symyx’s programs and technologies will be presented along with a discussion of the future prospects in the area. 9:45 Role of Sensors in Combinatorial Materials Research Radislav A. Potyrailo, PhD, Biosciences, Combichemistry and Characterization Technologies, Global Research Center, General Electric Company In the area of sensors, advances in component microfabrication, electronics, and data analysis stimulate the development of new concepts in combinatorial materials screening. These advances are already impacting several phases in a typical combinatorial discovery cycle that include parallel materials synthesis, their performance testing, evaluation of properties, and processing of collected data. Several examples from our work will demonstrate that sensors provide an attractive addition to the infrastructure of analytical instruments for materials screening. Our other examples will further highlight the applicability of sensors beyond combinatorial screening to take advantage of their capabilities on more traditional, i.e., laboratory and manufacturing, scales. 10:15 Gas Sensor System for Rapid Screening of Catalysts Oxidation Yusuke Yamada, PhD, Research Scientist, Special Division for Green Life Technology, National Institute of Advanced Industrial Science and Technology (AIST), Japan We will discuss the use of the gas sensor system for evaluation of the catalysts oxidation processes. The advantages of our gas sensors related with their small-size, rapid response, easy parallelization will be reviewed in comparison with other screening methods. The catalysts for CO combustion or selective oxidation of lower alkanes screened by suitable gas sensor system will be presented. The sensor system consisting of CO, CO2, and odor sensors which are for the quantification of CO, CO2, and aldehyde and ketone will be reviewed. 11:15 Miniaturization and Small Scale Properties Sensors in the High Throughput Materials Discovery Oleg Kolosov, PhD, Director, Innovation and Outreach, Symyx Technologies, Inc. A portfolio of sensing platforms in the field of catalysts, process liquids and polymers developed at Symyx Technologies is presented. Such real-time, in-situ sensors can function under broad temperature, high pressure and in chemically hostile environments. They allow to accurately measure the properties of materials and monitor miniaturized parallel reaction processes including density and viscosity of liquids and multiphase systems, thermal transitions as well as rheology, bulk compressibility and polymer density to mention a few. 11:45 Combinatorial Screening of Polymeric Coating Formulations Ali R. Mehrabi, PhD, Senior Research Engineer, Avery Research Center, Avery Dennison A combinatorial factory for preparation and screening of polymeric coating materials is developed. The coating formulations are prepared and coated using a novel combinatorial coating technique in order to obtain combinatorial libraries having various compositions and thickness. These combinatorial libraries are tested and screened using different high throughput methods. Examples of combinatorial screening of oxygen and moisture barrier coatings as well as pressure-sensitive adhesives are presented and their advantages and disadvantages are discussed. In collaboration with: J.Grunlan, D.L.Holguin, J.Akhave, Avery Dennison 12:15 Nanomechanical Properties Screening of Combinatorial Thin-Film Libraries by Nanoindentation Oden L. Warren, PhD, Director of R&D, Hysitron, Inc. The combinatorial methodology is efficient for creating thin-film libraries with controlled variations in film composition and/or film thickness. Because of the thin-film format, the corresponding variations in elastic modulus and hardness are best determined by the nanoindentation technique. This presentation focuses on using nanoindentation to differentiate shape-memory, superelastic, and austenitic compositions of compositional spreads of ternary alloys deposited onto silicon. The requirements for ensuring compatibility between thin-film libraries and the nanoindentation technique also will be addressed. Combi Technologies for Bio, Pharma and Nanomaterials 2:10 Chairperson's Remarks Yadunandan L. Dar, Corporate Research, National Starch and Chemical Company 2:15 Integration of Combinatorial Synthesis, Rapid Screening, and Computational Modeling in Biomaterials Design Joachim Kohn, PhD, Professor of Chemistry, Rutgers University and NJ Center for Biomaterials We describe (i) the use of parallel synthesis techniques to generate large libraries of polymers, (ii) rapid screening assays for the characterization of bio-relevant material properties, and (iii) predictive computational models of the biological response of cells in contact with biomaterials. The successful integration of these 3 methodologies provides the necessary framework for the acceleration of the development of new degradable polymers for medical applications. 2:45 New Crystalline Forms of Small Molecule Compositions 3:15 Rational Design in the Screening of Asymmetric Homogeneous Catalysis Alan A. Smith, PhD, Vice President Business Development, Avantium Chemicals With the ever increasing "time to market" pressure, the provision of rapid answers is an important need for pharmaceutical companies is a key need, today and tomorrow. The presentation will highlight some of the platforms developed by Avantium to address these issues, ranging from isomer separation by crystallization, polymorph screening, catalyst screening and process optimization. Specific emphasis will be given to Avantium Technologies Rational Screening techniques which allow for rapid identification of optimum conditions, avoiding time-consuming, trial and error experiments. This iterative cycle of descriptor calculation testing and empirical model building will be discussed and Avantium will share some developments in the field applied to asymmetric homogeneous catalysis. 4:15 Miniaturization of Chemical Synthesis to Enhance the Drug Discovery Process Paul Watts, PhD, Senior Scientist, Department of Chemistry, University of Hull, United Kingdom In this presentation a number of chemical reactions of pharmaceutical interest will be used to illustrate the advantages that micro reactors offer for the rapid optimisation of reactions, in which the product is typically produced in both higher yield and purity. It will be illustrated that compounds may be prepared and purified within an integrated system, in sufficient quantities for biological evaluation to be performed. Furthermore, it will be demonstrated that it is possible to generate intermediates in situ within the reactor, which may then be subsequently reacted to produce more complex products. It will also be shown that integration of the micro reactor to a highly sensitive microchannel-based biological assay system would enable rapid screening to be performed. 4:45 Novel Approach in Identification of Polymeric Vehicles for Enhanced Bioactive Delivery Miroslav Petro, PhD, Group Leader, Symyx Technologies, Inc. Polymers offer a great opportunity to precisely dial-in a desired set of performance features via a combination of its building blocks, i.e. monomers. We report on development of a generic workflow based on monitoring interactions of diverse polymers with a bioactive as well as with a biological substrate and aimed at discovery of molecular vehicles for targeted delivery of bioactives to human tissues. 5:15 Combinatorial Gradient Reference Specimens for Advanced Scanning Probe Nanometrology Michael J. Fasolka, PhD, NIST Combinatorial Methods Center A host of new scanning probe microscopy techniques promise the nanoscale mapping of chemical, physical, biological and electro-optical properties; however, these new methods generally provide untested and/or qualitative data. We will describe a new research effort at NIST aimed at producing combi-inspired reference specimens useful to the development, and eventual quantification, of these emerging imaging technologies. These specimens will help calibrate SPM image contrast, and help evaluate probe quality, thus advancing our abilities to characterize nano-materials, NEMS, nano-photonics and biomaterials.